Barzolvolimab for Chronic Urticaria

Recruiting at 75 trial locations

Overseen By Celldex Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celldex Therapeutics

Must be taking: H1-antihistamines

Disqualifiers: Pregnancy, Chronic spontaneous urticaria, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 20 weeks

196 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called barzolvolimab for people with chronic hives that don't improve with regular allergy medicine. The study aims to see if barzolvolimab can reduce or eliminate their symptoms by blocking the body's reaction that causes hives. Participants will receive different doses of the medication over several months, followed by an additional observation period.

Will I have to stop taking my current medications?

You will need to stay on your current second generation non-sedating H1-antihistamine medication throughout the trial.

What data supports the effectiveness of the drug barzolvolimab (CDX-0159) for chronic urticaria?

While there is no direct data on barzolvolimab, studies show that omalizumab, a similar type of drug, is effective in treating chronic urticaria, especially in patients who do not respond to standard treatments. Omalizumab works by targeting a part of the immune system involved in allergic reactions, which may suggest potential for barzolvolimab in similar conditions. ^{1 2 3 4 5}

How is the drug barzolvolimab different from other treatments for chronic urticaria?

Barzolvolimab is unique because it is a humanized antibody that targets and inhibits the KIT receptor, which is essential for mast cell function, thereby reducing skin mast cells and disease activity in chronic urticaria. This mechanism is different from other treatments like omalizumab, which targets IgE to prevent allergic reactions. ^{3 5 6 7 8}

Eligibility Criteria

This trial is for adults with Chronic Inducible Urticaria (hives) not relieved by antihistamines. Participants must have had symptoms for at least 6 weeks, use effective contraception, and be willing to maintain a symptom diary. Excluded are those with additional risky medical conditions, active infections like HIV or hepatitis B/C, other skin conditions, pregnant/nursing women, history of anaphylaxis or recent live vaccines.

Inclusion Criteria

I am willing to keep a daily electronic diary of my symptoms and attend all study visits.

I agree to use effective birth control during and for 5 months after the study.

You have a positive reaction during the skin test at both the screening and randomization visits.

Exclusion Criteria

I have a skin condition that is itchy in addition to chronic inducible urticaria.

I haven't had a live vaccine in the last 2 months and agree not to during the study.

Medical condition that would cause additional risk or interfere with study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive either barzolvolimab 150mg, 300mg, or placebo for 20 weeks

20 weeks

Subcutaneous injections every 4 or 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• barzolvolimab (CDX-0159)

Trial Overview The study tests barzolvolimab's effectiveness on hives unresponsive to H1-antihistamines. It involves comparing barzolvolimab against a placebo in terms of clinical effects and safety. The drug's behavior in the body will also be studied.

Participant Groups

Group I: barzolvolimab 300 mg in patients with Symptomatic Dermographism Experimental Treatment 1 Intervention

barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks

Group II: barzolvolimab 300 mg in patients with Chronic Inducible Cold Urticaria Experimental Treatment 1 Intervention

barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks

Group III: barzolvolimab 150 mg in patients with Symptomatic Dermographism Experimental Treatment 1 Intervention

barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks

Group IV: barzolvolimab 150 mg in patients with Chronic Inducible Cold Urticaria Experimental Treatment 1 Intervention

barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks

Group V: Placebo Comparator in patients with Chronic Inducible Cold Urticaria Placebo Group 1 Intervention

Placebo injection subcutaneous every 4 weeks for 20 weeks

Group VI: Placebo Comparator in patients with Symptomatic Dermographism Placebo Group 1 Intervention

Placebo injection subcutaneous every 4 weeks for 20 weeks

Who Is Running the Clinical Trial?

Celldex Therapeutics

Lead Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

Findings from Research

Omalizumab 300 mg significantly reduced symptoms of chronic idiopathic urticaria (CIU) compared to placebo, with a notable decrease in urticarial activity scores and itch severity scores across multiple studies involving 1117 patients.

The treatment also increased the percentage of angioedema-free days, indicating its efficacy in managing symptoms that are resistant to conventional antihistamine treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review. Carrillo, DC., Borges, MS., García, E., et al.[2023]

In a study of 878 French patients with chronic urticaria, omalizumab (OMA) showed a longer drug survival rate compared to previous studies, with 50% of patients still on treatment 2.4 years after starting.

The main reason for discontinuing OMA was achieving well-controlled disease in 50% of patients, but many were able to restart treatment, indicating its effectiveness in managing chronic urticaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. Litovsky, J., Hacard, F., Tétart, F., et al.[2023]

Barzolvolimab (CDX-0159) was well tolerated in patients with antihistamine-refractory chronic inducible urticaria, showing significant depletion of skin mast cells and reduction in serum tryptase levels, indicating effective systemic mast cell ablation.

The treatment led to complete responses in 95% of patients and significant improvements in urticaria control and quality of life, suggesting its potential as a therapeutic option for mast cell-mediated disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. Terhorst-Molawi, D., Hawro, T., Grekowitz, E., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review. [2023]

2. Turkey pubmed.ncbi.nlm.nih.gov

Effective treatment of different H1-antihistamine-refractory chronic urticaria phenotypes with omalizumab. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Long-term efficacy of fixed-dose omalizumab for patients with severe chronic spontaneous urticaria. [2015]

5. Spain pubmed.ncbi.nlm.nih.gov

Omalizumab is efficacious for management of recalcitrant, antihistamine-resistant chronic urticaria. [2017]

6. Spain pubmed.ncbi.nlm.nih.gov

Omalizumab in the treatment of chronic urticaria. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Immunological effects of omalizumab in chronic urticaria: a case report. [2015]

8. Denmark pubmed.ncbi.nlm.nih.gov

Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. [2023]